Evaluation of cell-free DNA approaches for multi-cancer early detection.

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology.

Influence of esomeprazole on the bioavailability of afatinib: A pharmacokinetic cross-over study in patients with non-small cell lung cancer.

Afatinib is an oral small-molecule kinase inhibitor (SMKI) approved for treatment of metastatic non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) driver mutation. Although oral administration is convenient, most SMKIs experience pH-dependent solubility. A drug-drug interaction between afatinib and proton-pump inhibitors (PPIs) has, however, never been studied in humans.

Characterization of DNA-protein complexes by nanoparticle tracking analysis and their association with systemic lupus erythematosus.

Nanotechnology enables investigations of single biomacromolecules, but technical challenges have limited the application in liquid biopsies, for example, blood plasma. Nonetheless, tools to characterize single molecular species in such samples represent a significant unmet need with the increasing appreciation of the physiological importance of protein structural changes at nanometer scale. Mannose-binding lectin (MBL) is an oligomeric plasma protein and part of the innate immune system through its ability to activate complement.

Search for rare decays of and Higgs bosons to and a photon in proton-proton collisions at = 13 .

A search is presented for decays of and Higgs bosons to a meson and a photon, with the subsequent decay of the to . The analysis uses data from proton-proton collisions with an integrated luminosity of 35.9 at collected with the CMS detector at the LHC.

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine.

Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors).

Brain Renin-Angiotensin System: Does It Exist?

Because of the presence of the blood-brain barrier, brain renin-angiotensin system activity should depend on local (pro)renin synthesis. Indeed, an intracellular form of renin has been described in the brain, but whether it displays angiotensin (Ang) I-generating activity (AGA) is unknown. Here, we quantified brain (pro)renin, before and after buffer perfusion of the brain, in wild-type mice, renin knockout mice, deoxycorticosterone acetate salt-treated mice, and Ang II-infused mice.

Stone-Mode Ultrasound for Determining Renal Stone Size.

Purpose: The purpose of this study was to measure the accuracy of stone-specific algorithms (S-mode) and the posterior acoustic shadow for determining kidney stone size with ultrasound (US) in vivo.

Materials And Methods: Thirty-four subjects with 115 renal stones were prospectively recruited and scanned with S-mode on a research US system. S-mode is gray-scale US adjusted to enhanced stone contrast and resolution by minimizing compression and averaging, and increasing line density and frequency.

Postoperative hyperoxia (60%) worsens hepatic injury in mice.

Background: Liver damage by ischemia and reperfusion injury is a risk factor for morbidity and mortality after liver surgery. Postoperative oxygen treatment is routinely applied in the postanesthesia and intensive care unit after liver surgery. The risks of aggravating the injury by increasing inspiratory oxygen from 21 to 60% in the postoperative period were investigated in mice.

High-level ab initio potential energy surfaces and vibrational energies of H2CS.

Six-dimensional (6D) potential energy surfaces (PESs) of H(2)CS have been generated ab initio using the recently proposed explicitly correlated (F12) singles and doubles coupled cluster method including a perturbational estimate of connected triple excitations, CCSD(T)-F12b [T. B. Adler, G.

Characterization of helper virus-independent cytopathogenic classical swine fever virus generated by an in vivo RNA recombination system.

Molecular analyses revealed that most cytopathogenic (cp) pestivirus strains evolve from noncytopathogenic (noncp) viruses by nonhomologous RNA recombination. In contrast to bovine viral diarrhea virus (BVDV), cp classical swine fever virus (CSFV) field isolates were rarely detected and always represented helper virus-dependent subgenomes. To investigate RNA recombination in more detail, we recently established an in vivo system allowing the efficient generation of recombinant cp BVDV strains in cell culture after transfecting a synthetic subgenomic and nonreplicatable transcript into cells being infected with noncp BVDV (A.

RNA recombination between persisting pestivirus and a vaccine strain: generation of cytopathogenic virus and induction of lethal disease.

Molecular analysis of a cytopathogenic (cp) bovine viral diarrhea virus (BVDV) isolate (1741) obtained from a case of mucosal disease (MD) led to the identification of five different viral subgenomic RNAs in addition to a noncytopathogenic (noncp) strain (NCP 1741). For each of the subgenomes, a large internal deletion was found together with an inserted sequence encoding part of ribosomal protein S27a fused to an N-terminally truncated ubiquitin monomer. Surprisingly, the two cellular insertions together with flanking viral sequences encoding parts of NS3 and NS4B are >99% identical to the previously described sequence of BVDV vaccine strain RIT (P.

Complete genomic sequence of border disease virus, a pestivirus from sheep.

The genus Pestivirus of the family Flaviviridae comprises three established species, namely, bovine viral diarrhea virus (BVDV), classical swine fever virus (CSFV), and border disease virus from sheep (BDV). In this study, we report the first complete nucleotide sequence of BDV, that of strain X818. The genome is 12,333 nucleotides long and contains one long open reading frame encoding 3, 895 amino acids.

Classical swine fever virus: recovery of infectious viruses from cDNA constructs and generation of recombinant cytopathogenic defective interfering particles.

The 5'- and 3'-terminal sequences of the genomic RNA from classical swine fever virus (CSFV) were determined, and the resulting information was used for construction of full-length CSFV cDNA clones. After transfection of in vitro-transcribed RNA derived from a cDNA construct, infectious CSFV was recovered from porcine cells. To confirm the de novo generation of infectious CSFV from cloned DNA, a genetically tagged CSFV was constructed.

Simian sarcoma virus-encoded gag-related protein: in vitro cleavage by Friend leukemia virus-associated proteolytic activity.

The simian sarcoma virus (SSV) encodes a gag-related 65,000-Da protein (SSV p65) which is not processed in SSV nonproducer cells (SSV-NP cells) (H.-J. Thiel, T.

Simian sarcoma virus transformation-specific glycopeptide: immunological relationship to human platelet-derived growth factor.

The simian sarcoma virus transformation-specific glycopeptide (SSV-TrSgp) represents a proteoglycan which is released from SSV-transformed cells and can be detected by an autologous goat serum against SSV nonproducer cells (SSV-NP serum) (H.-J. Thiel, R.

Partial characterization of a transformation-specific glycopeptide in SSV-NP cells.

An autologous antiserum against simian sarcoma virus-infected nonproducer cells (SSV-NP cells) recognized a SSV transformation-specific glycopeptide (SSV-TrSgp) [H.-J. Thiel, T.